Multiple machine learning methods and comparative transcriptomics identify pivotal genes for ischemia–reperfusion injury in human donor tissue undergoing orthotopic liver transplantation

Abstract

Abstract Background Hepatic ischemia–reperfusion injury (HIRI) is a major complication affecting patient prognosis during the period after orthotopic liver transplantation. Although an increasing number of scientists have investigated the molecular biology of ischemia–reperfusion injury during orthotopic liver transplantation in animal and cellular models in recent years, studies using comprehensive and high-quality sequencing results from human specimens to screen for key molecules are still lacking. Aims Exploring the molecular biological pathways and key molecules associated with HIRI during orthotopic liver transplantation through RNA sequencing and related bioinformatics analysis techniques. Methods By performing mRNA sequencing on liver tissue samples obtained from 15 cases of in situ liver transplantation patients who experienced ischemia and reperfusion injury within one year at Guizhou Medical University, and combining with bioinformatics analysis and machine learning methods, we identified the genes and transcription factors that are closely associated with ischemia-reperfusion injury during in situ liver transplantation surgery. Results There were 877 differentially expressed genes (DEGs) identified in the included liver samples, of which 817 DEGs were upregulated and 60 were downregulated. Functional enrichment analysis revealed significant enrichment of immune-related terms, such as inflammation, defense responses, responses to cytokines, immune system processes, and cellular activation. In addition, core gene enrichment analysis after cytoHubba screening suggested that liver reperfusion injury may be associated with translation-related elements as a pathway together with protein translation processes. Machine learning with the WGCNA screening method identified PTGS2, IRF1 and CDKN1A as key genes in the reperfusion injury process. Conclusions This study demonstrated that the pathways and genomes whose expression is altered throughout the reperfusion process may be critical for the progression of HIRI during orthotopic liver transplantation.